Effect of a treat-to-target intervention of cardiovascular risk factors on subclinical and clinical atherosclerosis in rheumatoid arthritis: a randomised clinical trial

2019 ◽  
pp. annrheumdis-2018-214075 ◽  
Author(s):  
Benjamin Burggraaf ◽  
Deborah F van Breukelen-van der Stoep ◽  
Marijke A de Vries ◽  
Boudewijn Klop ◽  
Anho H Liem ◽  
...  

BackgroundPatients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease (CVD). No long-term intervention trials on CVD risk factors have been published, and a debate on the efficacy of controlling traditional risk factors in RA is ongoing. We aimed to evaluate a treat-to-target approach versus usual care regarding traditional CVD risk factors in patients with RA.MethodsIn this open-label, randomised controlled trial, patients with RA aged <70 years without prior CVD or diabetes mellitus were randomised 1:1 to either a treat-to-target approach or usual care of traditional CVD risk factors. The primary outcome was defined as change in carotid intima media thickness (cIMT) over 5 years, and the secondary outcome was a composite of first occurrence of fatal and non-fatal cardiovascular events.ResultsA total of 320 patients (mean age 52.4 years; 69.7% female) with RA underwent randomisation and 219 patients (68.4%) completed 5 years of follow-up. The mean cIMT progression was significantly reduced in the treat-to-target group compared with usual care (0.023 [95% CI 0.011 to 0.036] mm vs 0.045 [95% CI 0.030 to 0.059] mm; p=0.028). Cardiovascular events occurred in 2 (1.3%) of the patients in the treat-to-target group vs 7 (4.7%) in those receiving usual care (p=0.048 by log-rank test).ConclusionThis study provides evidence on the benefit of a treat-to-target approach of traditional CVD risk factors for primary prevention in patients with well-treated RA.Trial registration numberNTR3873.

2020 ◽  
Vol 18 (5) ◽  
pp. 431-446 ◽  
Author(s):  
George E. Fragoulis ◽  
Ismini Panayotidis ◽  
Elena Nikiphorou

Rheumatoid arthritis (RA) is an autoimmune inflammatory arthritis. Inflammation, however, can spread beyond the joints to involve other organs. During the past few years, it has been well recognized that RA associates with increased risk for cardiovascular (CV) disease (CVD) compared with the general population. This seems to be due not only to the increased occurrence in RA of classical CVD risk factors and comorbidities like smoking, obesity, hypertension, diabetes, metabolic syndrome, and others but also to the inflammatory burden that RA itself carries. This is not unexpected given the strong links between inflammation and atherosclerosis and CVD. It has been shown that inflammatory cytokines which are present in abundance in RA play a significant role in every step of plaque formation and rupture. Most of the therapeutic regimes used in RA treatment seem to offer significant benefits to that end. However, more studies are needed to clarify the effect of these drugs on various parameters, including the lipid profile. Of note, although pharmacological intervention significantly helps reduce the inflammatory burden and therefore the CVD risk, control of the so-called classical risk factors is equally important. Herein, we review the current evidence for the underlying pathogenic mechanisms linking inflammation with CVD in the context of RA and reflect on the possible impact of treatments used in RA.


2021 ◽  
Vol 14 ◽  
pp. 117954412110287
Author(s):  
Mir Sohail Fazeli ◽  
Vadim Khaychuk ◽  
Keith Wittstock ◽  
Boris Breznen ◽  
Grace Crocket ◽  
...  

Objective: To scope the current published evidence on cardiovascular risk factors in rheumatoid arthritis (RA) focusing on the role of autoantibodies and the effect of antirheumatic agents. Methods: Two reviews were conducted in parallel: A targeted literature review (TLR) describing the risk factors associated with cardiovascular disease (CVD) in RA patients; and a systematic literature review (SLR) identifying and characterizing the association between autoantibody status and CVD risk in RA. A narrative synthesis of the evidence was carried out. Results: A total of 69 publications (49 in the TLR and 20 in the SLR) were included in the qualitative evidence synthesis. The most prevalent topic related to CVD risks in RA was inflammation as a shared mechanism behind both RA morbidity and atherosclerotic processes. Published evidence indicated that most of RA patients already had significant CV pathologies at the time of diagnosis, suggesting subclinical CVD may be developing before patients become symptomatic. Four types of autoantibodies (rheumatoid factor, anti-citrullinated peptide antibodies, anti-phospholipid autoantibodies, anti-lipoprotein autoantibodies) showed increased risk of specific cardiovascular events, such as higher risk of cardiovascular death in rheumatoid factor positive patients and higher risk of thrombosis in anti-phospholipid autoantibody positive patients. Conclusion: Autoantibodies appear to increase CVD risk; however, the magnitude of the increase and the types of CVD outcomes affected are still unclear. Prospective studies with larger populations are required to further understand and quantify the association, including the causal pathway, between specific risk factors and CVD outcomes in RA patients.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 475.2-476
Author(s):  
A. Osailan

Background:People with rheumatoid arthritis (RA) are at high risk for cardiovascular diseases (CVD) and CVD mortality. Reduced Chronotropic response (CR), which produces exercise intolerance, is known as a contributing factor to CVD and mortality. Studies have shown that people with RA have reduced CR. However, knowledge about the factors associated with CR in people with RA is limited.Objectives:To explore the factors associated with CR including CVD risk factors, inflammatory markers and cardiorespiratory fitness (VO2 peak).Methods:106 people with RA completed a treadmill exercise tolerance test while heart rate (HR) was monitored via 12 leads ECG. CR was defined as the percentage of [(achieved peak HR minus resting HR) divided by (age-predicted maximum HR minus resting HR)]. Serological CVD risk factors and inflammatory markers including lipids profile, markers of insulin resistance and sensitivity (HOMA, QUICKi), high sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), fibrinogen and white blood cells (WBC) were examined via a fasted blood sample. VO2 peak was assessed via breath-by-breath gas analysis.Results:34% had reduced CR based on the cut-off value (≤ 80%) and the average CR was 86.2 ± 21%. Body mass index (r=-0.33, p=.001), HOMA (r=-0.26, p=.009), hsCRP (r=-0.23, p=.02), ESR (r=-0.21, p=.04), fibrinogen (r=-0.2, p=.05), WBC (r=-0.21, p=.04) were inversely associated with CR, whereas, high density lipoprotein (HDL) (r=0.43, p<.001), QUICKi (r=0.31, p=.002), and VO2 peak (r=0.4, p<.001) were positively associated with CR. When all the variables were entered into a stepwise linear regression, HDL (p<.001) and VO2 peak (p=.009) were independently associated with CR.Conclusion:The current findings suggest that CR in RA was associated with many CVD risk factors, inflammatory markers, and cardiorespiratory fitness. Among all the varibales, HDL and cardiorespiratory fitness were moderately and independently associated with CR. Future studies should investigate the effect of improving these associated variables on CR in people with RA via exercise training programes.Acknowledgements:Thanks to physical activity in Rheumatoid arthritis research team and Research department in Dudley Hospital. Sincere appreciation and gratitude to Dr Jet Veldhuizen van Zanten, Prof. Joan Duda, and Prof. George Kitas from the University of Birmingham and Prof. George Metsios from the University of Wolverhampton.Disclosure of Interests:None declared


2019 ◽  
Vol 2 (2) ◽  
pp. 01-04
Author(s):  
Delcio G Silva Junior

The presence of Cardio Vascular Disease (CVD) impacts negatively on expectation and quality of life of the population, being one of the main causes of disability. Many of those who become cardiovascular patients throughout their life could have had different evolution if preventive attitudes were taken. Since 50’s decade, Framingham studies have shown the importance of predetermining factors for CVD occurrence. The classical CVD risk factors such as diabetes, metabolic syndrome, dyslipidemia, hypertension, smoking and family history are well established as predictors of cardiovascular events. The presence of Cardio Vascular Disease (CVD) impacts negatively on expectation and quality of life of the population, being one of the main causes of disability. Many of those who become cardiovascular patients throughout their life could have had different evolution if preventive attitudes were taken. Since 50’s decade, Framingham studies have shown the importance of predetermining factors for CVD occurrence. The classical CVD risk factors such as diabetes, metabolic syndrome, dyslipidemia, hypertension, smoking and family history are well established as predictors of cardiovascular events. However, in certain clinical conditions, traditional risk factors seem not to fully explain the incidence of CVD. Coronary artery disease and early atherosclerosis in young women with Systemic Lupus Erythematosus (SLE) are one of the best examples of how chronic inflammatory diseases can affect individuals who are normally poorly exposed to traditional risk factors. Even with the plurality of extra-articular manifestations of rheumatologic diseases, such as pulmonary hypertension and SLE encephalopathy, uveitis in spondyloarthritis, or as Achalasia in scleroderma, attention is being paid to the frequent cardiovascular system involvement in these patients, especially in the vascular territory


2017 ◽  
Vol 77 (1) ◽  
pp. 48-54 ◽  
Author(s):  
Cynthia S Crowson ◽  
Silvia Rollefstad ◽  
Eirik Ikdahl ◽  
George D Kitas ◽  
Piet L C M van Riel ◽  
...  

ObjectivesPatients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA.MethodsIn 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions.Results5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics).ConclusionsIn a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.


Circulation ◽  
2020 ◽  
Vol 141 (7) ◽  
pp. 592-599 ◽  
Author(s):  
Anandita Agarwala ◽  
Erin D. Michos ◽  
Zainab Samad ◽  
Christie M. Ballantyne ◽  
Salim S. Virani

Cardiovascular disease (CVD) is the leading cause of death among women in the United States. As compared with men, women are less likely to be diagnosed appropriately, receive preventive care, or be treated aggressively for CVD. Sex differences between men and women have allowed for the identification of CVD risk factors and risk markers that are unique to women. The 2018 American Heart Association/American College of Cardiology Multi-Society cholesterol guideline and 2019 American College of Cardiology/American Heart Association guideline on the primary prevention of CVD introduced the concept of risk-enhancing factors that are specific to women and are associated with an increased risk of incident atherosclerotic CVD in women. These factors, if present, would favor more intensified lifestyle interventions and consideration of initiation or intensification of statin therapy for primary prevention to mitigate the increased risk. In this primer, we highlight sex-specific CVD risk factors in women, stress the importance of eliciting a thorough obstetrical and gynecological history during cardiovascular risk assessment, and provide a framework for how to initiate appropriate preventive measures when sex-specific risk factors are present.


2020 ◽  
pp. bjophthalmol-2019-315333
Author(s):  
Juan E Grunwald ◽  
Maxwell Pistilli ◽  
Gui-Shuang Ying ◽  
Maureen G Maguire ◽  
Ebenezer Daniel ◽  
...  

PurposeChronic kidney disease (CKD) patients often develop cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess the association between progression of retinopathy and concurrent incidence of CVD events in participants with CKD.DesignWe assessed 1051 out of 1936 participants in the Chronic Renal Insufficiency Cohort Study that were invited to have fundus photographs obtained at two timepoints separated by 3.5 years, on average.MethodsUsing standard protocols, presence and severity of retinopathy (diabetic, hypertensive or other) and vessel diameter calibre were assessed at a retinal image reading centre by trained graders masked to study participants’ information. Participants with a self-reported history of CVD were excluded. Incident CVD events were physician adjudicated using medical records and standardised criteria. Kidney function and proteinuria measurements along with CVD risk factors were obtained at study visits.ResultsWorsening of retinopathy by two or more steps in the EDTRS retinopathy grading scale was observed in 9.8% of participants, and was associated with increased risk of incidence of any CVD in analysis adjusting for other CVD and CKD risk factors (OR 2.56, 95% CI 1.25 to 5.22, p<0.01). After imputation of missing data, these values were OR=1.66 (0.87 to 3.16), p=0.12.ConclusionProgression of retinopathy is associated with higher incidence of CVD events, and retinal-vascular pathology may be indicative of macrovascular disease even after adjustment for kidney diseases and CVD risk factors. Assessment of retinal morphology may provide important information when assessing CVD in patients with CKD.


2015 ◽  
Vol 42 (6) ◽  
pp. 935-942 ◽  
Author(s):  
Anna Södergren ◽  
Kjell Karp ◽  
Christine Bengtsson ◽  
Bozena Möller ◽  
Solbritt Rantapää-Dahlqvist ◽  
...  

Objective.This prospective followup study investigated subclinical atherosclerosis in relation to traditional cardiovascular disease (CVD) risk factors and inflammation in patients with rheumatoid arthritis (RA) recruited at diagnosis compared with controls.Methods.Patients diagnosed with early RA were consecutively recruited into a prospective study. From these, a subgroup aged ≤ 60 years (n = 71) was consecutively included for ultrasound measurement of intima-media thickness (IMT) and flow-mediated dilation (FMD) at inclusion (T0) and after 5 years (T5). Age- and sex-matched controls (n = 40) were also included.Results.In the Wilcoxon signed-rank test, both IMT and FMD were significantly aggravated at T5 compared to baseline in patients with RA, whereas only IMT was significantly increased in controls. In univariate linear regression analyses among patients with RA, the IMT at T5 was significantly associated with age, systolic blood pressure (BP), cholesterol, triglycerides, Systematic Coronary Risk Evaluation (SCORE), and Reynolds Risk Score at baseline (p < 0.05). Similarly, FMD at T5 was significantly inversely associated with age, smoking, systolic BP, SCORE, and Reynolds Risk Score (p < 0.05). A model with standardized predictive value from multiple linear regression models including age, smoking, BP, and blood lipids at baseline significantly predicted the observed value of IMT after 5 years. When also including the area under the curve for the 28-joint Disease Activity Score over 5 years, the observed value of IMT was predicted to a large extent.Conclusion.This prospective study identified an increased subclinical atherosclerosis in patients with RA. In the patients with RA, several traditional CVD risk factors at baseline significantly predicted the extent of subclinical atherosclerosis 5 years later. The inflammatory load over time augmented this prediction.


2017 ◽  
Vol 42 (3) ◽  
pp. 326-332 ◽  
Author(s):  
Parvin Mirmiran ◽  
Zahra Bahadoran ◽  
Azita Zadeh Vakili ◽  
Fereidoun Azizi

Limited data are available regarding the association of major dietary patterns and risk of cardiovascular disease (CVD) in Middle Eastern countries. We aimed to evaluate the association of major dietary patterns, using factor analysis, with the risk of CVD. Participants without CVD (n = 2284) were recruited from the Tehran Lipid and Glucose Study and were followed for a mean of 4.7 years. Dietary intake of participants was assessed at baseline (2006–2008); biochemical variables were evaluated at baseline and follow-up examination. Multivariate Cox proportional hazard regression models, adjusted for potential confounders, were used to estimate risk of CVD across tertiles of dietary pattern scores. Linear regression models were used to indicate association of dietary pattern scores with changes of CVD risk factors over the study period. Two major dietary patterns, Western and traditional, were identified. During a mean 4.7 ± 1.4 years of follow-up, 57 participants experienced CVD-related events. In the fully adjusted model, we observed an increased risk of CVD-related events in the highest compared to the lowest tertile category of Western dietary pattern score (HR = 2.07, 95% CI = 1.03–4.18, P for trend = 0.01). Traditional dietary pattern was not associated with incidence of CVD or CVD risk factors. A significant association was observed between the Western dietary pattern and changes in serum insulin (β = 5.88, 95% CI = 0.34–11.4). Our findings confirm that the Western dietary pattern, characterized by higher loads of processed meats, salty snacks, sweets, and soft drinks, is a dietary risk factor for CVD in the Iranian population.


2019 ◽  
Vol 8 (11) ◽  
pp. 2011
Author(s):  
Fang-I Hsieh ◽  
Hung-Yi Chiou ◽  
Chaur-Jong Hu ◽  
Jiann-Shing Jeng ◽  
Huey-Juan Lin ◽  
...  

Ischemic stroke (IS) is multifactorial causation combining with traditional cardiovascular disease (CVD) and genetic risk factors. Combined effects of MMP-7, MMP-8 and MMP-26 on the risk of IS remain incompletely understood. We aimed to assess individual and joint effects for IS risk by weighted genetic risk score (wGRS) from these three genes and traditional CVD risk factors. A case-control study including 500 cases with IS and 500 stroke-free healthy controls frequency-matched with cases by age and sex was conducted. The wGRS was a weighted average of the number of risk genotype across selected SNPs from MMP-7, MMP-8 and MMP-26. Multivariate logistic regression models were used to analyze the relationship between wGRS and risk of IS. A wGRS in the second tertile was associated with a 1.5-fold increased risk of IS compared with the lowest tertile after adjusting for traditional CVD risk factors. Compared to subjects with low genetic and low modifiable CVD risk, those with high genetic and high modifiable CVD risk had the highest risk of IS (adjusted-OR = 5.75). In conclusion, higher wGRS was significantly associated with an increased risk for IS. A significant interaction between genetic and traditional CVD risk factors was also found on the risk of IS.


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